Identification and validation of cholesterol homeostasis and NK cell-associated predictive and therapeutic models for Coronary atherosclerotic heart disease patients with ST-elevated myocardial infarction: Insights from artificial intelligence and multi-omics
6 affiliations
- 1Geriatrics Department, Shapingba District Traditional Chinese Medicine Hospital, Chongqing 400030, China
- 2Preventive Medicine Center, Shapingba District Traditional Chinese Medicine Hospital, Chongqing 400030, China
- 3Preventive Medicine Center, Yubei District Traditional Chinese Medicine Hospital, Chongqing 401120, China
- 4Department of Cardiovascular Medicine, Chongqing Municipality Traditional Chinese Medicine Hospital Chongqing, Chongqing 400021, China
- 5Department of Oncology, Shapingba District Traditional Chinese Medicine Hospital, Chongqing 400030, China
- 6Department of Cardiology and Neurology, Shapingba District Traditional Chinese Medicine Hospital, Chongqing 400030, China. Electronic address: [email protected]
Abstract
OBJECTIVE: Dysregulation of Cholesterol homeostasis(CH) and NK cells proportion can increase risk of ST-Elevated Myocardial Infarction(STEMI) for Coronary atherosclerotic heart disease(CAD) patients. Hence, it is necessary for the investigation of CH and MC in pathogenesis of STEMI for CAD patients, providing additional choice for the prevention of STEMI for CAD patients. METHODS: By combining 5 peripheral blood bulk profiles of CAD patients with STEMI and integrative bioinformatic pipelines, such as ssGSEA, CIBERSORT, WGCNA, machine learning, consensus clustering, we first identified novel CH and NK cell(NCH)-associated molecular subgroup and hub genes for CAD patients with STEMI, and then estimated hub genes predictive performance for STEMI onset among CAD patients. Besides, the biological features of hub gene were estimated both in bulk and single-cell profiles of CAD patients with STEMI, especially in artificial intelligence(AI)-driven virtual cells. Indeed, AI-empowered therapeutic enrichment framework(DrugRefLector) and molecular docking were cross-performed for identification of optimal preventative agents targeting hub genes for CAD patients. Finally, in vitro study confirmed the differentially expressed level of hub genes. RESULTS: Integrated NCH can lead to the molecular stratification for CAD patients with AMI, which provides insights into the patient precision medicine. Besides, NAMPT and CLEC4D can be considered as up-regulated NCH-associated hub gene involved in STEMI pathogenesis of CAD patients with satisfied predictive efficacy, which was mainly distributed at NK cells. Novelty, BRD-K92455082 can be considered as optimal STEMI-preventative agent for the CAD patients by targeting NAMPT and CLEC4D. CONCLUSION: Our study provides integrative evidence suggesting a potential combined role of cholesterol homeostasis and NK cell-associated transcriptional programs of AMI for CAD patients, which offers novel insights into patient precision and personalized medicine.
Related
- Mycobacterium tuberculosis inactivates host oxysterols to impair macrophage cholesterol homeostasis
- Multivariate Genomic Analysis Reveals Shared Genetic Architecture and Potential Therapeutic Targets for Atherosclerotic Cardiovascular Disease
- ERK5 Signaling and Ferroptosis in Bone Homeostasis: Emerging Connections and Therapeutic Perspectives
- Multi-objective artificial pedosphere intelligence for microbial homeostasis-oriented governance of functional nanoparticle systems in complex ecosystems
- Potency of nucleoside analogs against Powassan virus replication and identification of 4'-fluorouridine as a therapeutic candidate for tick-borne orthoflavivirus encephalitis
BibTeX
@article{chen2026identification,
title = {{Identification and validation of cholesterol homeostasis and NK cell-associated predictive and therapeutic models for Coronary atherosclerotic heart disease patients with ST-elevated myocardial infarction: Insights from artificial intelligence and multi-omics}},
author = {Xuemei Chen and Yifan Zhao and Xixi Guo and Qiushan Man and Ming Wang and Zhou Wang and Jun Cheng and Shijian Chen},
journal = {Computational Biology and Chemistry},
year = {2026},
month = may,
doi = {10.1016/j.compbiolchem.2026.109103},
url = {https://doi.org/10.1016/j.compbiolchem.2026.109103},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Identification and validation of cholesterol homeostasis and NK cell-associated predictive and therapeutic models for Coronary atherosclerotic heart disease patients with ST-elevated myocardial infarction: Insights from artificial intelligence and multi-omics
AU - Xuemei Chen
AU - Yifan Zhao
AU - Xixi Guo
AU - Qiushan Man
AU - Ming Wang
AU - Zhou Wang
AU - Jun Cheng
AU - Shijian Chen
PY - 2026
DA - 2026/05/14
JO - Computational Biology and Chemistry
DO - 10.1016/j.compbiolchem.2026.109103
UR - https://doi.org/10.1016/j.compbiolchem.2026.109103
AB - OBJECTIVE: Dysregulation of Cholesterol homeostasis(CH) and NK cells proportion can increase risk of ST-Elevated Myocardial Infarction(STEMI) for Coronary atherosclerotic heart disease(CAD) patients. Hence, it is necessary for the investigation of CH and MC in pathogenesis of STEMI for CAD patients, providing additional choice for the prevention of STEMI for CAD patients. METHODS: By combining 5 peripheral blood bulk profiles of CAD patients with STEMI and integrative bioinformatic pipelines, such as ssGSEA, CIBERSORT, WGCNA, machine learning, consensus clustering, we first identified novel CH and NK cell(NCH)-associated molecular subgroup and hub genes for CAD patients with STEMI, and then estimated hub genes predictive performance for STEMI onset among CAD patients. Besides, the biological features of hub gene were estimated both in bulk and single-cell profiles of CAD patients with STEMI, especially in artificial intelligence(AI)-driven virtual cells. Indeed, AI-empowered therapeutic enrichment framework(DrugRefLector) and molecular docking were cross-performed for identification of optimal preventative agents targeting hub genes for CAD patients. Finally, in vitro study confirmed the differentially expressed level of hub genes. RESULTS: Integrated NCH can lead to the molecular stratification for CAD patients with AMI, which provides insights into the patient precision medicine. Besides, NAMPT and CLEC4D can be considered as up-regulated NCH-associated hub gene involved in STEMI pathogenesis of CAD patients with satisfied predictive efficacy, which was mainly distributed at NK cells. Novelty, BRD-K92455082 can be considered as optimal STEMI-preventative agent for the CAD patients by targeting NAMPT and CLEC4D. CONCLUSION: Our study provides integrative evidence suggesting a potential combined role of cholesterol homeostasis and NK cell-associated transcriptional programs of AMI for CAD patients, which offers novel insights into patient precision and personalized medicine.
SN - 1476-9271
SN - 1476-928X
ER -